Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa
Purpose: Retinitis pigmentosa (RP) belongs to a group of inherited retinal diseases with high genetic heterogeneity. This study aimed at identifying the disease-causing variants in patients with autosomal recessive RP. Methods: Three RP families with autosomal recessive inheritance and 139 sporad...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Molecular Vision
2019-01-01
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| Series: | Molecular Vision |
| Subjects: | |
| Online Access: | http://www.molvis.org/molvis/v25/35/ |
| _version_ | 1818752904723431424 |
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| author | Xiaoqiang Xiao Yingjie Cao Shaowan Chen Min Chen Xiaoting Mai Yuqian Zheng Tsz Kin Ng Haoyu Chen |
| author_facet | Xiaoqiang Xiao Yingjie Cao Shaowan Chen Min Chen Xiaoting Mai Yuqian Zheng Tsz Kin Ng Haoyu Chen |
| author_sort | Xiaoqiang Xiao |
| collection | DOAJ |
| description | Purpose: Retinitis pigmentosa (RP) belongs to a group of inherited retinal diseases with high genetic heterogeneity. This study aimed at identifying the disease-causing variants in patients with autosomal recessive RP.
Methods: Three RP families with autosomal recessive inheritance and 139 sporadic RP patients were included. Complete ophthalmic examinations were conducted in all the study subjects. DNA samples were extracted from patients’ peripheral blood for whole exome sequencing (WES) analysis. Direct Sanger sequencing was conducted for validating the identified mutations and cosegregation pattern in the RP families.
Results: One novel (c.7492G>C:p.Ala2498Pro and c.8422C>T:p.Ala2808Thr) and one reported (c.8012T>A:p.Leu2671X and 6416G>A:p.Cys2139Tyr) pair of compound heterozygous mutations, as well as one reported compound homozygous mutation (c.6416G>A:p.Cys2139Tyr/c.8012T>A:p.Leu2671X), were identified in the EYS gene from three families with autosomal recessive RP. All the mutations were cosegregated with the RP phenotype in the RP families. For the sporadic RP patients, seven novel and seven reported EYS variants were identified in 19 patients, including two novel frameshift (c.8301dupT:p.Asp2767fs and c.9437_9440del:p.Glu3146fs), three novel missense (c.8297G>C:p.Gly2766Ala, c.9052T>C:p.Trp3018Arg, and c.8907T>G:p.Cys2969Trp), and one nonsense (c.490C>T:p.Arg164X) variants. All the novel mutations were confirmed by Sanger sequencing. Most of the variants were located at the C-terminus of the EYS protein. Bioinformatics analyses indicated that all detected variants were damaging or possibly damaging.
Conclusions: This study identified eight novel EYS variants and expanded the spectrum of EYS mutations in Chinese RP patients. |
| first_indexed | 2024-12-18T04:58:53Z |
| format | Article |
| id | doaj.art-790bb45c09b84523b81863eb255af083 |
| institution | Directory Open Access Journal |
| issn | 1090-0535 1090-0535 |
| language | English |
| last_indexed | 2024-12-18T04:58:53Z |
| publishDate | 2019-01-01 |
| publisher | Molecular Vision |
| record_format | Article |
| series | Molecular Vision |
| spelling | doaj.art-790bb45c09b84523b81863eb255af0832022-12-21T21:20:12ZengMolecular VisionMolecular Vision1090-05351090-05352019-01-012513546Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosaXiaoqiang Xiao0Yingjie Cao1Shaowan Chen2Min Chen3Xiaoting Mai4Yuqian Zheng5Tsz Kin Ng6Haoyu Chen7Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, ChinaJoint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, ChinaJoint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, ChinaJoint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, ChinaJoint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, ChinaJoint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, ChinaShantou University Medical College, Shantou, Guangdong, China; and Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong KongJoint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, ChinaPurpose: Retinitis pigmentosa (RP) belongs to a group of inherited retinal diseases with high genetic heterogeneity. This study aimed at identifying the disease-causing variants in patients with autosomal recessive RP. Methods: Three RP families with autosomal recessive inheritance and 139 sporadic RP patients were included. Complete ophthalmic examinations were conducted in all the study subjects. DNA samples were extracted from patients’ peripheral blood for whole exome sequencing (WES) analysis. Direct Sanger sequencing was conducted for validating the identified mutations and cosegregation pattern in the RP families. Results: One novel (c.7492G>C:p.Ala2498Pro and c.8422C>T:p.Ala2808Thr) and one reported (c.8012T>A:p.Leu2671X and 6416G>A:p.Cys2139Tyr) pair of compound heterozygous mutations, as well as one reported compound homozygous mutation (c.6416G>A:p.Cys2139Tyr/c.8012T>A:p.Leu2671X), were identified in the EYS gene from three families with autosomal recessive RP. All the mutations were cosegregated with the RP phenotype in the RP families. For the sporadic RP patients, seven novel and seven reported EYS variants were identified in 19 patients, including two novel frameshift (c.8301dupT:p.Asp2767fs and c.9437_9440del:p.Glu3146fs), three novel missense (c.8297G>C:p.Gly2766Ala, c.9052T>C:p.Trp3018Arg, and c.8907T>G:p.Cys2969Trp), and one nonsense (c.490C>T:p.Arg164X) variants. All the novel mutations were confirmed by Sanger sequencing. Most of the variants were located at the C-terminus of the EYS protein. Bioinformatics analyses indicated that all detected variants were damaging or possibly damaging. Conclusions: This study identified eight novel EYS variants and expanded the spectrum of EYS mutations in Chinese RP patients.http://www.molvis.org/molvis/v25/35/Retinitis pigmentosa |
| spellingShingle | Xiaoqiang Xiao Yingjie Cao Shaowan Chen Min Chen Xiaoting Mai Yuqian Zheng Tsz Kin Ng Haoyu Chen Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa Molecular Vision Retinitis pigmentosa |
| title | Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa |
| title_full | Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa |
| title_fullStr | Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa |
| title_full_unstemmed | Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa |
| title_short | Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa |
| title_sort | whole exome sequencing reveals novel eys mutations in chinese patients with autosomal recessive retinitis pigmentosa |
| topic | Retinitis pigmentosa |
| url | http://www.molvis.org/molvis/v25/35/ |
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